CERN Project I: Clinical Trials

Dr. Mark Gilbert offered to sit down with us to educate us and provide updates on the progress and efforts of Project I, whose central focus is Clinical Trials.

Mission:

To rapidly formulate new clinical trials to be performed in multiple Centers of Excellence within the CERN group to evaluate new treatment options for patients with ependymoma.

Goal:

Develop new and better treatments for patients while ensuring that there is proper management and maintenance of function, and quality of life.

CERN Foundation Network:

The CERN Foundation’s adult clinical trial network is currently comprised of eight institutions located within the United States, all of whom are considered experts in the treatment of adult brain tumors, with specific interest and even greater expertise in ependymoma. There are an additional nine pediatric institutions, including Canada with similar expertise in ependymoma. The CERN Foundation clinical trials network is in the process of expanding our reach even further to Europe with the expectation that within the next year we will have CERN centers in both France and Italy.

CERN Foundation Clinical Trials: Adult and Pediatric Populations

Thus far, the CERN Foundation clinical trials have focused on patients diagnosed with recurring ependymoma. There are a number of factors that we consider when creating a clinical trial for patients both on the adult and pediatric side. First, we look at safety and efficacy of a particular treatment, then functional capabilities are taken into consideration, and finally, quality of life is a major component of the evaluation.

We currently have two adult clinical trials open to the public CERN 08-02 and CERN 09-02. The first study, CERN 08-02 combines two drugs: Temozolomide (Temodar) an oral chemotherapy agent that is widely used in tumors of the CNS (central nervous system). Temodar is known to be very well tolerated, easy to administer and has the added benefit of being able to cross the blood brain barrier (BBB). In this trial, we combined Temodar with a 2nd chemotherapy agent known as Tykerb (Lapatinib). The CERN Foundation team chose Lapatinib for its ability to target specific proteins on the surface of cancer cells. These proteins are involved in molecular pathways that help sustain the cancer cells and promote their growth. Research performed by Dr. Richard Gilberston and Dr. Ken Aldape, both Co-Principal Investigators at the CERN Foundation, demonstrated that two important proteins, ERB1 and ERB2 are often highly expressed in ependymomas, both of which are targeted by Lapatinib.

Therefore, the logical combination of the established chemotherapy agent, Temodar, with targeted molecule, Lapatinib was used to create the first CERN Foundation adult clinical trial. As this study is nearing completion, we are hopeful that we will be able to present the results this year at one of our international meetings.

In addition to the CERN Foundation adult clinical trial CERN 08-02, we have created a 2nd CERN Foundation adult clinical trial, CERN 09-02. This trial combines Carboplatin, a chemotherapy agent that is considered standard treatment for ependymoma, with a second chemotherapy agent known as Bevacizumab (Avastin). Avastin is known to block the formation of blood vessels in cancer. This study is currently open and actively accruing patients with recurring ependymoma.

On the pediatric side of the CERN Foundation, our team has initiated a CERN Foundation pediatric clinical trial, CERN 08-01 (link), which combines Lapatinib and Avastin. The goal of this trial in the pediatric population is to utilize the vessel blocking activity of Avastin along with the molecular targeting ability of Lapatinib. This study has completed accrual for the 1st stage and is planned for presentation at the upcoming Pediatric Society of Neuro-oncology meeting.

At the CERN Foundation, we are constantly monitoring all of the clinical trials for safety. We routinely monitor our patients to ensure that early results of effectiveness are meeting, or exceeding expectations. However, we do not prematurely release or publish these results as this would compromise the integrity of the clinical trial.

Of note, Temodar was not chosen for the pediatric study because, unlike in adults, it has shown less benefit in pediatric brain tumors. We do not yet know the reason for the lowered benefit in the pediatric population.

Clinical Trials: What’s on the horizon?

On the adult side, we will continue the further development of selected drugs from the laboratory screening due to the efforts of our colleagues in Project III. Once we have completed accrual for CERN 08-02, we will focus our efforts on completion of accrual for CERN 09-02. Once both clinical trials have completed accrual, we feel confident that we will have developed a state of the art scientifically based protocol that will incorporate the most promising chemo therapy drugs for this disease.

The Pediatric network will soon be opening a clinical trial for patients with ependymoma that utilizes a chemotherapy agent that showed great promise during laboratory testing, using very specific ependymoma models. This agent, fluorouracil (5-FU), has been extensively tested by the CERN Foundation Investigators, and through these studies they have determined the optimal treatment regimen. This regimen has undergone safety testing in a study performed at St. Jude and will soon be incorporated into the CERN Foundation pediatric clinical trials.

In addition, new treatments are being evaluated similar to that described above for future adult studies.

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